System for confocal imaging within dermal tissue

ABSTRACT

An improved system for confocal imaging within dermal tissue of a patient is provided which minimizes instability in confocal images by reducing the relative motion of the tissue with respect to the confocal imaging optics of the system. The system includes a mechanism for maintaining an area of skin tissue under stress by application of force at the edges of the area, and an imaging head coupled to this mechanism for imaging the stressed skin. The mechanism includes a mechanical structure, such as a platen, brace, or attachment, which both supports the imaging head of the system and applies stress to a limited surface area of the tissue to minimize skin motion during confocal imaging.

This application claims the benefit of priority from co-pending U.S.Provisional Application Ser. No. 60/028,847, filed Oct. 18, 1996.

FIELD OF THE INVENTION

The present invention relates to a confocal imaging system for in vivoclinical examinations of dermal and subdermal tissues, and particularlyto a confocal imaging system of a patient's skin tissue which minimizesinstability in confocal images by reducing the relative motion of thetissue with respect to the confocal imaging optics of the system. Thisinvention is especially suitable for providing an instrument orattachment for dermal pathological applications.

BACKGROUND OF THE INVENTION

Systems have been proposed for confocal scanning of skin, such asdescribed in Rajadhyaksha et al., “In vivo Confocal Scanning LaserMicroscopy of Human Skin: Melanin provides strong contrast,” The Journalof Investigative Dermatology, Volume 104, No. 6, June 1995, pages 1-7.These systems have confocal optics which direct light to the patient'sskin tissue and image the returned reflected light. Such optics have alimited field of view of the patient's skin tissue, which for examplemay cover a tissue area less than one millimeter wide. One problem withthese systems is that motion of the patient during confocal imaging cancause the tissue area being imaged to move relative to the system'sconfocal optics, shifting the field of view of the tissue area withrespect to the optics. Consequently, confocal images from such systemsmay appear unstable to the viewing physician, making it difficult forthe physician to observe dermal structures of interest. Even slightmotion of the patient's skin tissue, such as due to involuntary musclemovement in adjacent tissue or from a circulatory pulse, can causedermal structures of a confocal image to appear to move in and out ofthe imaged tissue area.

SUMMARY OF THE INVENTION

Accordingly, it is the principal object of the present invention toprovide an improved system for confocal imaging within dermal andsubdermal tissue of a patient which minimizes instability in confocalimages by reducing the relative motion of the tissue with respect to theconfocal imaging optics of the system.

It is another object of the present invention to provide an improvedsystem for confocal imaging of tissue having a mechanical structure,such as a platen, brace, or attachment which both supports the confocalimaging optics of the system and applies stress to a limited surfacearea of the tissue to minimize skin motion during confocal imaging.

Briefly described, the system embodying the present invention includes amechanism for maintaining an area of skin tissue under stress byapplication of force at the edges of the area, and an imaging headcoupled to this mechanism for imaging the stressed skin. The mechanismand imaging head provide an integrated assembly. In one embodiment, themechanism of the system for maintaining an area of skin tissue understress is provided by a platen, which is positionable with respect tothe patient having the skin tissue to be examined. The imaging head iscoupled to the platen and is positioned for imaging through an orificein the platen. To position the platen with respect to the patient, thepatient is supported by a table and the platen rides in a carriage uponrails over the patient. The carriage and platen assembly may betemporarily locked in position upon the rails. Another mechanism isprovided in the system for moving the platen from an up position in thecarriage, where the platen is spaced from the patient, to a downposition onto the surface of the skin tissue of the patient, such thatin the down position the force of the platen stresses the skin-tissuewithin the orifice of the platen.

In a second embodiment, the mechanism of the system for maintaining anarea of skin tissue under stress is provided by a brace supporting theimaging head. The brace has an opening through which the imaging headimages the skin tissue. The brace is restrained by straps to the bodypart of the patient having the skin tissue in order to force the braceagainst the skin tissue, thereby stressing the skin tissue within theopening of the brace. The brace may further include an upper lamination,coupled to the imaging head, and a lower lamination, coupled to therestraining straps, which provides the opening of the brace. The lowerlamination has slots for receiving the upper lamination in which theupper lamination is movable within the slots over the lower laminationand temporarily fixable within respect to the lower lamination. Theupper lamination has an aperture (or window) substantially smaller thanthe opening in the lower lamination. Through the aperture of the upperlamination, the imaging head images the stressed skin tissue within theopening of the lower lamination.

In a third embodiment, the mechanism of the system for maintaining anarea of skin tissue under stress is provided by an attachment having aninner window member and a flexible diaphragm member extending radiallyfrom the inner member. A suction mechanism is provided for creating avacuum between the attachment and the surface of the skin tissue toforce the skin tissue against the inner member, thereby stressing theskin tissue adjacent to the inner member. The imaging head images thestressed skin tissue through the window member. The diaphragm member mayfurther include a semi-rigid ring along its outer periphery and anannular protruding section which defines inner and outer cavities whenthe attachment is adjacent to the skin tissue. The suction mechanism maythen selectively create suction in the inner and outer cavities, whenthe attachment is adjacent to the skin tissue, to pull the skin tissueinto the cavities and stress the skin tissue adjacent to the innermember.

The three embodiments of the system are particularly suitable forimaging external tissue in different regions of the patient's body. Theplaten may be used for confocal imaging of skin tissue on the chest orback. The brace may be used for gross anatomical features, such as thearm, leg or torso, around which the straps can hold the brace upon. Theattachment is useful for smaller regions of the skin, where there is nogross anatomical feature, or where the surface of the skin tissue in notsubstantially level.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing objects, features and advantages of the invention willbecome more apparent from a reading of the following description inconnection with the accompanying drawings in which:

FIG. 1 is a side view of the system in accordance with a firstembodiment of the present invention having the platen of the system in adown position;

FIG. 2 is a plan view of the system of FIG. 1;

FIG. 3 is a front view of the system of FIG. 1 without the subjectpatient;

FIG. 4 is a perspective view of the platen of the system of FIG. 1;

FIG. 5 is a side view of the system in accordance with a secondembodiment of the present invention;

FIG. 6 is a front view of the system of FIG. 5 without the subject skintissue;

FIG. 7 is a plan view of the system of FIG. 5 without the subject skintissue;

FIG. 8 is a perspective view of the brace structure of the system ofFIG. 5 with the upper lamination of the brace structure and confocalimaging head removed;

FIG. 9 is a perspective view of the system in accordance with a thirdembodiment of the present invention;

FIG. 10 is a cross-sectional view of the system along line 10-10 of FIG.9 when the attachment of the system is not engaging skin tissue; and

FIG. 11 is another cross-sectional view of the system along line 10-10of FIG. 9 when the attachment of the system is engaging skin tissue.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIGS. 1-4, there is shown system 14 including a rigid table16 with a pad 17 on table surface 16 a upon which a patient 18 may layflat. Pad 17 may be composed of a vinyl-covered cell foam (such as CF40100 Foam from EAR Specialty Composites of Indianapolis. Ind.) whichdeforms under the weight of patient 18 and remains deformed for a periodof time after the patient has left the table. Table 16 has two parallelrails 20 spaced apart from each other along two opposite sides of table16, and two parallel rails 22 spaced apart from each other. Rails 20 and22 are perpendicular to each other, i.e., rails 20 extend in the xdirection and rails 22 extend in the y direction.

A platen 30 carrying a confocal imaging head 34 is mounted in amechanism provided by rails 20 and 22 for movably positioning head 34 toobserve dermal tissue of interest in the body of patient 18. Thismechanism has a carriage 25 supporting platen 30. Carriage 25 ridesalong rails 22 across table 16 (as indicated by bidirectional arrow x),and is locked in position with respect to rails 22 by a lock 28, such asa locking screw. Rails 22 and its two spacers 23, which connect rails 22together, ride along rails 20 up or down table 16 (as indicated bybi-directional arrow y), and are locked in position with respect torails 20 by a lock 24, such as a locking screw. Thus, platen 30 can thenbe moved by the operator in two orthogonal directions x and y overpatient 18 and temporarily fixed in a desired position.

Referring to FIG. 4, platen 30 and the head 34 assembly is shown in moredetail. Platen 30 is a rigid structure having an upper surface 31 with atranslation stage 36 which is mechanically coupled to a confocal imaginghead 34 via support 36 a. Confocal imaging head 34 has an objective lens35 positioned over an orifice or opening 32 through platen 30. Confocalimaging head 34 with objective lens 35 are described in U.S. applicationSer. No. 08/650,684, filed May 20, 1996 and assigned to the sameassignee as the present invention, and is herein incorporated byreference. Translation stage 36 is movable in two orthogonal directionsx′ and y′ (see arrows x′ and y′ in FIG. 4) to provide fine resolutionpositioning (as compared with coarse positioning of platen 30 via rails20 and 22) of imaging head 34, and more specifically objective lens 35,with respect to platen 30 over orifice 32. The translation stage 36 hascross rotating ball bearings (not shown) or cross piezoelectric positionactuators to facilitate fine resolution movement in orthogonaldirections x′ and y′. Manual stage micrometers 37 a and 37 b adjusttranslation stage 36 in x′ and y′ directions, respectively. Micrometers37 a and 37 b may be substituted by motors which are remotelycontrolled. A lock (not shown) on translation stage 36 may be providedto temporarily fix the position of stage 30, and consequently imaginghead 22, with respect to platen 30. Thus, translation stage 36 defines ameans for fine resolution positioning of the objective lens over theorifice. Also, an index matching plate 38 may be positioned withinorifice 32 in front of objective lens 35 to form a window whichmaintains the height stability of the tissue while presenting the edgesof orifice 32 to the skin for stressing the tissue.

Platen 30 includes four vibration damping rods 40 at the four corners ofplaten 30 (for purposes of illustration only two rods 40 are shown inFIG. 4). Each damping rod 40 has a lower end coupled to platen 30 and anupper end coupled to carriage 25, as shown in FIGS. 1-3. Thus, dampingrods 40 connect platen 30 to carriage 25. Damping rods 40 may behydraulic type shock absorbers which when released allow platen 30 togradually move from an up position to a down position upon the patient'sskin 14 a (such as shown in FIG. 1) and also allow platen 30 to be movedfrom a down position back to an up position. Locking screws (not shown)on the damping rods 40 may fix the position of platen 30 with respect tocarriage 25 in either up or down positions. Damping rods 40 therebyprovide a means for moving platen 30 from an up position, in which theplaten is spaced from patient 18, to a down position onto surface 18 aof skin tissue of the patient.

In operation of system 14, the operator (e.g., a physician) moves rails22 (i.e., the rails upon which carriage 25 rides) along rails 20 toposition platen 30 in the y direction, and moves carriage 25 along rails22 to position platen 30 in the x-direction such that the volume of skintissue of interest on patient 18, such as a lesion, will be positionedwithin orifice 23 of the platen when platen 30 is in a down position.Using locks 24 and 28 described above, the operator locks carriage 25with respect to rails 20 and 22, thus fixing the position of platen 30with respect to patient 18. Next, the operator releases damping rods 40to allow platen 30 to gradually fall by the force of gravity onto thepatient's skin. In response to the weight of platen 30, the skin lyingwithin orifice 32 of platen 30 bulges upwards into orifice 32, therebyapplying stress to the skin. This stress places the skin in orifice 32preferably under tension, but may further push the skin up into orifice32 by compression of skin beneath platen 30. The stress applied to theskin in orifice 32 is substantially due to the downward pressure orforce of platen 30 at the edges of orifice 32. Optionally, springs maybe located within damping rods 40 to provide additional downwardpressure onto the skin. The operator then controls the translation stagemovement either directly or remotely to position objective lens 35 ofimaging head 34 over area of tissue within orifice 32 desired to beimaged. The operator enables optics within the confocal imaging head toconfocally image horizontal, vertical, or angular sections throughdifferent planes of the tissue. During confocal imaging, the stressapplied to the skin tissue in orifice 32 stabilize the tissue reducingmotion of the skin tissue with respect to confocal imaging head 34,thereby stabilizing confocal images scanned by head 34.

Platen 30 may have a paper pad 42 to provide a recording media, and apen or marker 44 mechanically coupled to translation stage 36 by arm 43such that pen 44 is suspended over pad 42. Movement of translation stage36 can thus be recorded by ink from the pen 44 on pad 32. This allowsthe operator during confocal imaging by imaging head 34 to map thehorizontal extent or borders of a lesion in the skin, since pen 44transfers the motion of translation stage 36 on pad 43 by the fixedgeometry which mechanically couples pen 44 to objective lens 23 via arm43, stage 36, support 36 a and imaging head 34. After confocal imagingis complete, imaging head 34 may be replaced by another pen to permitthe operator to trace the extent of the lesion recorded on pad 32 ontothe surface of the skin.

Further, when platen 30 is in a down position, the operator can placeindex marks on the skin surface with a pen, or other marking instrument,at notches (not shown) along the sides of orifice 32. These index markslocate both orifice 32 and the relative position of objective lens 35with respect to the skin surface when confocal imaging is performed. Insubsequent examinations, orifice 32 and objective lens 35 can be alignedwith these index marks to confocally image the same area of skin, and,for example, observe changes occurring in a skin lesion over time.

A second embodiment of the present invention is shown in FIGS. 5-8having a system 58. System 58 includes a brace structure 50 having arigid lower lamination 52 which is held stationary to the skin tissue 18a of patient 18 by straps 54. Lower lamination 52 is shaped toapproximate the curvature of a gross anatomical body part of thepatient, such as part of the leg, torso, or arm, as shown in FIG. 5. Abottom 52 a of lower lamination 52 has an opening 53, as shown in FIGS.7 and 8. Bottom 52 a defines a well 59 therein between ends 57 a andsides 57 b of lower lamination 52. Ends 57 a and sides 57 b define arigid frame 57. Further, ends 57 a and sides 57 b have blind slots 55within which an upper lamination 56 is captured. FIG. 8 shows frame 57of lower lamination 52 in which upper lamination 56 has been removed forpurposes of illustration.

Upper lamination 56 is a curved rigid sheet parallel with lowerlamination 52, and has a confocal viewing window 58 (FIG. 7)substantially smaller than opening 53. Viewing window 58 may bepositioned at a location over opening 53 by sliding upper lamination 56over lower lamination 52 via slots 55 within frame 57. A confocalimaging head 60 is supported on brace structure 50 by gussets 62 (FIG.6) and has an objective lens (not shown) positioned for imaging throughconfocal viewing window 58 of upper lamination 56. The window maycontain a transparent plate for tissue height stabilization. Confocalimaging head 60 with objective lens 35 are described in U.S. applicationSer. No. 08/650,684, filed May 20, 1996 and assigned to the sameassignee as the present invention, and is herein incorporated byreference. Confocal imaging head 60 is fixably attached to upperlamination 56 and slides therewith over lower lamination 52.

In operation of system 58, brace 50 is first strapped by straps 54 overan anatomical feature, such as an arm, leg, or torso, in which thegeneral skin tissue area to be confocally imaged bulges upward throughopening 53 of bottom 52 a under the pressure from lower lamination 52,thereby applying stress to the surface of the skin. This stresspreferably places the skin through opening 53 under tension, but mayfurther push the skin up into opening 53 by compression of skin beneathlower lamination 52. The stress applied to the skin in opening 53 issubstantially due to the pressure or force from lower lamination 52 tothe skin tissue at the edges of opening 53. The specific area of theskin to be confocally imaged is then positioned within confocal viewingwindow 58 by sliding upper lamination 56 over lower lamination 52. Lowerlamination 52 provides a sliding surface for upper lamination 56 andslots 55 of frame 57 provide sufficient friction against upperlamination 56 to temporarily fix the position of upper lamination 56with respect to lower lamination 52 and the skin tissue. Confocalimaging head 60 is then attached to upper lamination 56 of brace 50 toposition the confocal optics of head 60, i.e., its objective lens,through confocal imagine window 58. When enabled, these confocal opticswithin imaging head 60 can confocally image horizontal, vertical, orangular sections through different planes of the tissue through confocalviewing window 58. Thus, brace 50 locates confocal imaging head 60 infixed relationship with the skin tissue, and window 58 defines anaperture through brace 50 for imaging via optics of head 60.

By attaching imaging head 60 to upper lamination 56, head 60 moves withmotion of the skin tissue since such motion is transferred to head 60via brace structure 50. This reduces the relative motion of the tissueheld under stress with respect to the confocal optics of imaging head 60to minimize instability of the confocal images from imaging head 60.Upper lamination 56 may be moved to reposition the confocal imagingoptics of head 60 through window 58 for confocal imaging of other areasof skin tissue within opening 53.

A third embodiment of the present invention is shown in FIGS. 9-11. Thisembodiment is provided by a tissue stabilization system 68 whichincludes an attachment 69. The tissue is shown at 84 in FIGS. 10-11 as alayer of skin. Attachment 69 includes a flexible diaphragm member 70, acentral circular window or plate member 72, and a semi-rigid ring 74.Diaphragm 70 is composed of deformable rubber selected to be lesscompliant than tissue 84. Diaphragm 70 radially extends from window 72outward to semi-rigid ring 74. Ring 74 may be composed of hard rubber,while window 72 may be composed of a material having an optical indexapproximately matching tissue 84. Diaphragm 70 has between ring 74 andwindow 72 an annular protruding section 75 (protruding in the directionof the arrow of FIG. 10). Section 75 defines outer and inner annularcavities 76 and 78, respectively. Also, attachment 69 has a pair ofvacuum lines 80 which each connects different ones of annular cavities76 and 78 to a pneumatic pump which selectively creates suction betweendiaphragm 70 and the surface 84 a of tissue 84. The size or diameter ofsystem 68 and its attachment 69 may be appropriately dimensioned for theskin surface area to be confocally imaged through window 72.

System 68 further includes a confocal imaging head 82 having anobjective lens 83 positioned such that lens 83 is directed to window 72of attachment 69. Confocal imaging head 60 with objective lens 35 aredescribed in U.S. application Ser. No. 08/650,684, filed May 20, 1996and assigned to the same assignee as the present invention, and isherein incorporated by reference. Objective lens 83 is shown in phantomlines in FIG. 9, and the dotted lines in the figure represent theoptical imaging paths between lens 83 and other confocal optics withinimaging head 82. For example, these optical imaging paths may beprovided within an extending snout between head 82 and objective lens83.

In operation, attachment 69 is first placed over surface 84 a of tissue84 such that diaphragm protruding section 75 is adjacent to surface 84a, as shown in FIG. 10. When window 72 is located over the area oftissue 84 to be confocally imaged, the air is evacuated via vacuum lines80 from each cavity 76 and 78. This creates suction which pulls tissue84 up into cavities 76 and 78, as shown in FIG. 11. As a result,semi-rigid ring 74 and window 72 are pulled downward onto surface 84,and the tissue beneath window 72 is placed under stress, such as bytension or compression. In this mode, attachment 69 engages or adheresby suction to the surface 84 a of the tissue.

Next, objective lens 83 of confocal imaging head 82 is placed againstwindow 72 for confocal imaging of tissue 84 below window 72, then theconfocal optics within imaging head 60 are enabled to provide confocalimages of horizonal, vertical and angular sections through differentplanes of the tissue. Optionally, attachment 69 may be fixedly attachedto head 82 in front of its objective lens 83 prior to placing attachment69 adjacent to the skin tissue. Since the tissue being confocally imagedis held under stress by attachment 69 under window 72, the relativemotion of this tissue with respect to the confocal optics within imaginghead 82 is reduced, thereby stabilizing confocal images from head 82.When imaging is complete, air is allowed to flow back into cavities 76and 78 via vacuum lines 80, allowing attachment 69 to disengage from thesurface 84 a of the tissue.

Alternatively, a liquid on the surface 84 a of the tissue may beevacuated via vacuum lines 80 (in combination with or instead of air)from cavities 76 and 78. Such a liquid may be applied to the surface 84a of the tissue prior to placing attachment 69 over the surface.

Each of the three embodiments of the present invention is particularlysuitable for imaging external tissue in different regions of thepatient's body. The first embodiment may be used for confocal imaging ofskin tissue on the chest or back, while the second embodiment may beused, for gross anatomical features, such as the arm or leg, aroundwhich straps can hold brace structure 50 upon. Further, the thirdembodiment is useful for smaller regions of the skin, particularly wherethere is no gross anatomical feature, or where the surface of the skintissue in not substantially level, such as the cervix or forehead. Eachof the above confocal imaging system embodiments provides a mechanismfor maintaining an area of skin tissue being confocal imaged under astressed configuration by tension or compression, thereby minimizing themotion of this area with respect to a confocal imaging head. In thecervix the tissue being imaged is not skin as that term is commonlyunderstood, but represents internal tissue of a patient. Internaltissues, for example which are surgically exposed, may be stabilizedusing the invention.

From the foregoing description, it will be apparent that there have beenprovided several embodiments of a confocal imaging system fordermatological pathology applications. Variations and modifications ofthe herein described system and other applications for the inventionwill undoubtedly suggest themselves to those skilled in the art.Accordingly, the foregoing description should be taken as illustrativeand not in a limiting sense.

1-26. (canceled)
 27. A system for recording on a recording medium thelocation of tissue sections in which the microscope has optics throughwhich the microscope images tissue, said system comprising: means formoving at least said optics in one or more directions during imaging toview different parts of said tissue with said microscope; and means,coupled to said moving means, for recording information about one ormore locations in the tissue of one or more imaged tissue sections on arecording medium.
 28. The system according to claim 27 furthercomprising means for applying said recording information onto thesurface of said tissue.
 29. The system according to claim 27 furthercomprising means for stabilizing said tissue to said optics.
 30. Thesystem according to claim 27 wherein said recorded information iscapable of mapping an extent of a lesion in said imaged tissue.
 31. Thesystem according to claim 27 wherein said recording medium is disposedon a platen stationary with respect to said tissue being imaged, andsaid recording means is movable with respect to said recording medium toenabling recording of said information.
 32. The system according toclaim 27 wherein said means for moving comprises a stage coupled to saidoptics for moving said optics in one or more directions during imagingto view said tissue with said microscope.
 33. The system according toclaim 32 wherein said stage has one or more micrometers to manuallycontrol the stage to position said optics in said one or moredirections.
 34. The system according to claim 32 wherein said stage isremotely controlled by motors to position said optics in said one ormore directions.
 35. The system according to claim 32 wherein said meansfor recording comprises a pen or marker mechanically coupled to saidstage to be movable in accordance with movement of said stage, said penor marker being disposed with respect to said recording medium to applyink to said recording medium to record one or more locations of saidoptics with respect to said imaged tissue.
 36. A method for recording ona recording medium the location of tissue sections in which themicroscope has optics through which the microscope images tissue, saidmethod comprising the steps of: moving at least said optics in one ormore directions during imaging to view different parts of said tissuewith said microscope; and recording on a recording medium one or morelocations in the tissue of one or more imaged tissue sections.
 37. Themethod according to claim 36 further comprising the step of applyingsaid recording information onto the surface of said tissue.
 38. Themethod according to claim 36 wherein said recorded one or more locationsmaps an extent of a lesion in said imaged tissue.
 39. An apparatus forrecording on a recording medium the location of tissue sections in whichthe microscope has optics through which the microscope images tissue,said apparatus comprising: a recording medium disposed on a platenpositionally related to the surface of the tissue; and a pen or markermechanically coupled to said optics, in which said pen or marker iscapable of recording position of said optics with respect to said tissueon said recording medium.
 40. The apparatus according to claim 39wherein said optics comprise an objective lens.